OBJECTIVE: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP.
DATA SOURCES: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms.
STUDY SELECTION AND DATA EXTRACTION: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design.
DATA SYNTHESIS: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting.
CONCLUSIONS: Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has a gene that makes it resistant to methicillin, as well as to other beta-lactam antibiotics, including flucloxacillin, beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, and carbapenems. MRSA can be part of the normal body flora (colonisation), especially in the nose, but it can cause infection, particularly in people with prolonged hospital admissions, with underlying disease, or after antibiotic use. About 8% of S aureus in blood cultures in England, Wales, and Northern Ireland is resistant to methicillin.
METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of selected treatments for MRSA infections at any body site? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS: At this update, searching of electronic databases retrieved 312 studies. After deduplication and removal of conference abstracts, 133 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 55 studies and the further review of 78 full publications. Of the 78 full articles evaluated, 15 systematic reviews and one subsequent RCT were added at this update. In addition, six studies were added to the Comment sections. We performed a GRADE evaluation for 12 PICO combinations.
CONCLUSIONS: In this systematic overview we categorised the efficacy for five interventions, based on information about the effectiveness and safety of cephalosporins (ceftobiprole, ceftaroline), daptomycin, linezolid, quinupristin-dalfopristin, pristinamycin (streptogramins), and tigecycline.
La diarrea aguda es la enfermedad más común que afecta a los viajeros, principalmente aquellos que se dirigen a regiones de alto riesgo. El uso de probióticos podría prevenir su aparición, sin embargo, los datos que apoyan su uso no son consistentes y no se recomiendan en las guías clínicas actuales. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos, identificamos cuatro revisiones sistemáticas que en conjunto incluyen siete estudios aleatorizados pertinentes a esta pregunta. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los probióticos podrían prevenir la diarrea del viajero, pero la certeza de la evidencia es baja.
The rationale for the use of probiotics in the management of infectious diseases is supported by their potential to influence and stabilize the composition of gut microbiota, enhance colonization resistance, and modulate immune function parameters. A literature review was conducted to determine the efficacy of using probiotics in selected infections: 1) infectious diarrhea in infants and children, 2) traveler's diarrhea, 3) necrotizing enterocolitis in infants, 4) Helicobacter pylori infection, 5) respiratory tract infections in adults and children, 6) ear, nose, and throat infections, and 7) infectious complications in surgical and critically ill patients. The different types of infections that have been subject to clinical studies with different probiotics obviously prevent any generic conclusions. Furthermore, the lack of consistency among studies focusing on 1 specific infection, in study design, applied probiotic strains, outcome parameters, and study population, along with the still limited number of studies, preclude clear and definite conclusions on the efficacy of probiotics and illustrate the need for better-aligned study designs and methodology. Exceptions were the management of infectious diarrhea in infants and traveler's diarrhea, antibiotic-associated diarrhea, and necrotizing enterocolitis. Sufficient consistent data exist for these applications to conclude that certain probiotics, under certain conditions, and in certain target populations, are beneficial in reducing the risk of infection. In addition, some evidence exists, although conclusions are premature, for the management of Helicobacter pylori infection and possible reduction of treatment side effects. Certain probiotics may also reduce the risk of various symptoms of respiratory tract infections in adults and children, including ear, nose, and throat infections, although data are currently far too limited to distill any clinical recommendations in this area. Positive but also negative results have been obtained in prevention of infectious complications in surgical and critically ill patients. For future studies it is recommended that researchers provide adequate power, identify pathogens, and report both clinical outcomes and immune biomarkers relating to putative underlying mechanisms.
To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP.
DATA SOURCES:
A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms.
STUDY SELECTION AND DATA EXTRACTION:
All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design.
DATA SYNTHESIS:
Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:
Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting.
CONCLUSIONS:
Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.
